Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders

@article{Akbarian2006MolecularAC,
  title={Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders},
  author={Schahram Akbarian and Hsien-Sung Huang},
  journal={Brain Research Reviews},
  year={2006},
  volume={52},
  pages={293-304}
}
GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders
TLDR
Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.
GAD1 Gene Expression in Blood of Patients with First-Episode Psychosis
TLDR
Further correlation and validation work between brain regions, cerebrospinal fluid and peripheral blood expression profiling are required to provide a better understanding of GAD25 and GAD67.
The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders
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Understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+.
Altered expression of genes involved in GABAergic transmission and neuromodulation of granule cell activity in the cerebellum of schizophrenia patients.
TLDR
The findings suggest that GABA transmission is decreased in the cerebellar cortices in individuals with schizophrenia and additional gene expression changes may reflect an attempt to increase GABA neurotransmission at the Cerebellar glomerulus.
The Impact of Oxidative Stress on GAD67 Levels and Parvalbumin-Positive Neurons
TLDR
A large preclinical and cognitive literature suggests that a dysfunctional frontal GABAergic network is associated to abnormal electroencephalographic spectra, which are thought to underlie higher cognitive functions and are known to be disturbed in schizophrenia.
GAD1 mRNA Expression and DNA Methylation in Prefrontal Cortex of Subjects with Schizophrenia
TLDR
Results suggest that chromatin remodeling mechanisms are involved in dysregulated GABAergic gene expression in schizophrenia, with a significant, on average 8-fold deficit in repressive chromatin-associated DNA methylation at the promoter.
Cortical Glutamic Acid Decarboxylase 67 Expression in Schizophrenia: Defining the Deficit
TLDR
An extensive characterization of the GAD67 deficit in schizophrenia is provided, and novel evidence of a functional impairment in PV neurons that may underlie cognitive deficits is provided.
Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT
TLDR
The results support the importance of genetic variation in GAD1 and COMT in regulating prefrontal cortical GABA function, and the directionality of the effects is inconsistent with earlier evidence of decreased GABA activity in schizophrenia.
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A substantial dysregulation of GAD mRNA expression in schizophrenia is suggested and, taken together with the results of protein expression studies, raise the possibility that both cortical and subcortical GABA function may be compromised in the disease.
GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss
TLDR
Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss, suggesting that the gene encoding GAD67 may be a common risk factor for schizophrenia.
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Although the results are negative, this was the first study to investigate GAD genes in schizophrenia, and further studies of these genes, particularly with schizophrenia subtypes, may prove valuable.
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The selective down-regulation of RELN and GAD(67) in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypotheses that these changes may be liability factors underlying psychosis.
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TLDR
Pharmacological principles that raise GAD67 expression levels could represent novel targets for antipsychotic therapy and could be a surrogate marker for psychosis liability.
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The inhibition of histone deacetylases could represent a pharmacological intervention mitigating epigenetically induced vulnerability to schizophrenia in individuals at risk.
Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia.
TLDR
The hypothesis that the expression of the 2 isoforms of GAD, 65 kd and 67 kd, is differentially affected in the hippocampus in schizophrenia and bipolar disorder is tested and a region-specific deficit of G AD(65) and GAD(67) mRNA expression is found in bipolar disorder.
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